Pathophysiological effects of long-term acid suppression in man

Area of Science:

• Gastroenterology
• Endocrinology
• Oncology

Background:

• Prolonged low stomach acid states impact gastric structure and function.
• Ageing, pernicious anemia, and Helicobacter pylori infection are key factors influencing gastric health.
• Atrophic gastritis and intestinal metaplasia are associated with precancerous lesions and gastric cancer.

Purpose of the Study:

• To critically evaluate the effects of prolonged low acid states on human stomach structure and function.
• To examine various human models, including ageing, pernicious anemia, and drug-induced states.
• To assess the relationship between gastric changes, endocrine cell hyperplasia, and cancer risk.

Main Methods:

• Review of available human evidence on prolonged low acid states.
• Examination of human models including ageing, pernicious anemia, and Zollinger-Ellison syndrome.
• Analysis of data related to H2 antagonists and omeprazole therapy.

Main Results:

• Ageing affects gastric acid output differently in men and women; atrophy is linked to reduced function and increased cancer risk.
• Pernicious anemia causes complete acid loss, hypergastrinemia, and endocrine cell hyperplasia; ECL-cell carcinoids and gastric cancer occur in 3-7% of cases.
• H2 antagonists may increase gastrin but show limited data on hyperplasia; omeprazole increases gastrin and is associated with endocrine cell hyperplasia in some patients.

Conclusions:

• Atrophic gastritis, often linked to H. pylori and ageing, is a significant risk factor for precancerous lesions and gastric cancer.
• While rare, gastric ECL-cell carcinoids can occur in pernicious anemia and Zollinger-Ellison syndrome, often related to hypergastrinemia.
• Long-term acid suppression therapy requires further investigation regarding endocrine cell hyperplasia and potential cancer risks.